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simultaneously typing nine serotypes of enteroviruses associated with hand, foot, and mouth disease by a gexp analyzer-based multiplex reverse transcription-pcr assay.hand, foot, and mouth disease (hfmd) is a contagious enteroviral disease occurring primarily in young children and caused by enterovirus 71 (ev71), coxsackievirus a16 (cva16), and other serotypes of coxsackievirus and echovirus. in this study, a gexp analyzer-based multiplex reverse transcription (rt)-pcr assay (gexp assay) consisting of chimeric primer-based pcr amplification with fluorescent labeling and capillary electrophoresis separation was developed to simultaneously identify nine serotyp ...201122116146
Emergence and transmission pathways of rapidly evolving evolutionary branch c4a strains of human enterovirus 71 in the central plain of china.Large-scale outbreaks of hand, foot, and mouth disease (HFMD) occurred repeatedly in the Central Plain of China (Shandong, Anhui, and Henan provinces) from 2007 until now. These epidemics have increased in size and severity each year and are a major public health concern in mainland China.201122125635
immunogenicity of a truncated enterovirus 71 vp1 protein fused to a newcastle disease virus nucleocapsid protein fragment in mice.enterovirus 71 (ev71) is one of the viruses that cause hand, foot and mouth disease. its viral capsid protein 1 (vp1), which contains many neutralization epitopes, is an ideal target for vaccine development. recently, we reported the induction of a strong immune response in rabbits to a truncated vp1 fragment (nt-vp1t) displayed on a recombinant newcastle disease virus (ndv) capsid protein. protective efficacy of this vaccine, however, can only be tested in mice, since all ev71 animal models thu ...201121978156
in vitro activity of paris polyphylla smith against enterovirus 71 and coxsackievirus b3 and its immune modulation.enterovirus 71 (ev71) and coxsackievirus b3 (cvb3) have resulted in severe pathogenesis caused by the host's immune response, including the cytokine cascade. paris polyphylla smith is a folk medicinal plant in asia traditionally prescribed for the reduction of pain and elimination of poisoning. in this study, we investigated the anti-ev71 and cvb3 activity of p. polyphylla smith as well as its immune modulation. the ic(50) for the p. polyphylla smith 95% ethanol extract against ev71 and cvb3 wer ...201122083992
comparing enterovirus 71 with coxsackievirus a16 by analyzing nucleotide sequences and antigenicity of recombinant proteins of vp1s and vp4s.enterovirus 71 (ev71) and coxsackievirus a16 (ca16) are two major etiological agents of hand, foot and mouth disease (hfmd). ev71 is associated with severe cases but not ca16. the mechanisms contributed to the different pathogenesis of these two viruses are unknown. vp1 and vp4 are two major structural proteins of these viruses, and should be paid close attention to.201122050722
[study on the prevalence of acute flaccid paralysis and hand foot mouth disease in beijing 2006 - 2008].to study the prevalence of acute flaccid paralysis (afp) and hand foot mouth disease (hfmd) in beijing, from 2006 - 2008.201121933539
in vitro inhibition of influenza virus infection by a crude extract from isatis indigotica root resulting in the prevention of viral attachment.isatis indigotica root (iir) has been widely used as a chinese medicinal herb to treat regular seasonal influenza over the long history of traditional chinese medicinal practice. however, its inhibitory activities against influenza virus infections along with the associated mechanisms have not been investigated comprehensively. in this study, the chemical nature, mode of action and in vitro anti-influenza activities of a crude extract ( ...201122179315
identification of bpr3p0128 as an inhibitor of cap-snatching activities of influenza virus.the aim of this study was to identify the antiviral mechanism of a novel compound, bpr3p0128. from a large-scale screening of a library of small compounds, bpr3p compounds were found to be potent inhibitors of influenza viral replication in madin-darby canine kidney (mdck) cells. bpr3p0128 exhibited inhibitory activity against both influenza a and b. the 50% inhibitory concentrations were in the range of 51-190 nm in mdck cells as measured by inhibition of cytopathic effect assays. bpr3p0128 app ...201121930871
[experts consensus on rescue and treatment of severe cases with enterovirus 71 (ev71) infection]. 201122176902
sustained high levels of interleukin-6 contribute to the pathogenesis of enterovirus 71 in a neonate mouse model.enterovirus 71 (ev71) is the major causative agent of hand, foot, and mouth disease (hfmd) in young children and has been consistently associated with the most severe complications of the disease, including central nervous system inflammation and pulmonary edema. increasing frequency and amplitude of ev71 outbreaks have raised awareness and concerns worldwide. previous reports proposed that overwhelming virus replication combined with the induction of massive proinflammatory cytokines is respons ...201121228224
molecular epidemiology of the 2005 enterovirus 71 outbreak in central taiwan.since 1998, taiwan has experienced annual outbreaks of enterovirus 71 (ev71) nationwide. the area around taichung city experienced a particularly large outbreak in 2005, after which ev71 disappeared for 2 y before re-emerging in 2008. here we present the clinical, genotypic, and epidemiological baseline data for the 2005 taichung outbreak.201121231813
mechanism of action of the suppression of influenza virus replication by ko-ken tang through inhibition of the phosphatidylinositol 3-kinase/akt signaling pathway and viral rnp nuclear export.ko-ken tang (kkt, aka kakkon-to), a conventional chinese herbal medicine, has been used for the treatment of the common cold, fever and influenza virus infection. however, the underlying mechanism of its activity against influenza virus infection remains elusive. in this study, the antiviral effect and its underlying mechanism was evaluated, including the investigation of anti-influenza virus activity of kkt on mdck cells and corresponding mechanism related to phosphatidylinositol 3-kinase (pi3k ...201121232589
neonatal rhesus monkey is a potential animal model for studying pathogenesis of ev71 infection.data from limited autopsies of human patients demonstrate that pathological changes in ev71-infected fatal cases are principally characterized by clear inflammatory lesions in different parts of the cns; nearly identical changes were found in murine, cynomolgus and rhesus monkey studies which provide evidence of using animal models to investigate the mechanisms of ev71 pathogenesis. our work uses neonatal rhesus monkeys to investigate a possible model of ev71 pathogenesis and concludes that this ...201121262515
an enterovirus 71 epidemic in guangdong province of china, 2008: epidemiological, clinical, and virogenic manifestations.enterovirus 71 (ev71) is shown to be a major causative agent in outbreaks of hand, foot, and mouth disease (hfmd) reported in guangdong (gd) province of china in 2008. a total of 48,876 hfmd cases (131 severe and 21 fatal) were reported to the gd hfmd web-based surveillance system, which covers 871 clinics. the main causes of death included central nervous system damage, heart failure, and pulmonary edema. the incidence rate was 52 per 100,000, and the epidemic peak appeared in may and june. ev7 ...201121266750
enterovirus 71 modulates a cox-2/pge2/camp-dependent viral replication in human neuroblastoma cells: role of the c-src/egfr/p42/p44 mapk/creb signaling pathway.enterovirus 71 (ev71) has been shown to induce cyclooxygenase-2 (cox-2) expression in human neuroblastoma sk-n-sh cells through the action of mapks, nf-?b, and ap-1. on the other hand, the transcription factor creb has also been implicated in the expression of cox-2 in other cell lines. here, we report that ev71-induced cox-2 expression and pge(2) production were both inhibited by pretreatment with the pka inhibitor h89 or by transfection with creb sirna. in addition, ev71-induced cox-2 expressi ...201121268077
detection, characterization and quantitation of coxsackievirus a16 using polyclonal antibodies against recombinant capsid subunit proteins.coxsackievirus a16 (cva16), together with enterovirus type 71 (ev71), is responsible for most cases of hand, foot and mouth disease (hfmd) worldwide. recent findings suggest that the recombination between cva16 and ev71, and co-circulation of these two viruses may have contributed to the increase of hfmd cases in china over the past few years. thus, for cva16, further understanding of its virology, epidemiology and development of diagnostic tests and vaccines are of importance. the present study ...201121295614
enterovirus 71 induces degradation of trim38, a potential e3 ubiquitin ligase.the tripartite motif (trim) proteins are a family of more than 70 members in human. however, only a few of them have been well studied. the trim proteins contain the conserved ring, b-box, coiled-coil, and spry domains, most of which are involved in protein ubiquitination. trim38 is a member of the trim protein family, which we studied in more detail here as its functions are largely unknown.201121306652
potent inhibition of human enterovirus 71 replication by type i interferon subtypes.enterovirus 71 (ev71) infection can induce a series of syndromes including herpangina, viraemia, hand-foot-and-mouth disease and even death. outbreaks of ev71 infection have been reported periodically over the world and have caused a great number of casualties and a high medical expenditure. some interferons (ifns) have been used for the treatment of viral infections for decades; however, conventional ifns only display mild anti-ev71 activities. no effective drug is currently available for the t ...201121311108
formaldehyde-inactivated human enterovirus 71 vaccine is compatible for co-immunization with a commercial pentavalent vaccine.in this study we tested the effectiveness of a formaldehyde-inactivated ev71 vaccine and its compatibility for co-immunization with a pentavalent vaccine that contained inactivated poliovirus (pv) vaccine. the inactivated ev71 vaccine (c2 genogroup) elicited an antibody response which broadly neutralized homologous and heterologous genogroups, including b4, c4, and b5. pups from vaccinated dams were resistant to the ev71 challenge and had a high survival rate and a low tissue viral burden when c ...201121315698
generation of murine monoclonal antibodies which cross-neutralize human enterovirus genogroup b isolates.a live enterovirus 71 (ev71) isolate designated, ev71/e59, with genotype b4 produced in vero cells and purified over a sucrose gradient was used as the immunogen to generate ev71-specific murine monoclonal antibodies. four hybridoma clones derived from the fusion of splenocytes of ev71/e59-preimmunized balb/c (h-2(d)) mice and the ns-1 myeloma cells that exhibit stable growth were selected for detailed characterization. the proof that the hybridomas produced are indeed true independent clones wa ...201121315763
onychomadesis outbreak in valencia, spain associated with hand, foot, and mouth disease caused by enteroviruses.this report evaluates the june 2008 onychomadesis outbreak in valencia, spain. the study sample consisted of 221 onychomadesis cases and 77 nonaffected individuals who lived close to those affected. we collected data on dietary variables, hygiene products, and individual pathological histories. feces and blood specimens were collected from 44 cases and 24 controls to evaluate exposure to infectious agents. pathological background data revealed a high frequency (61%) of hand, foot, and mouth dise ...201120553401
enterovirus 71 induces integrin ß1/egfr-rac1-dependent oxidative stress in sk-n-sh cells: role of ho-1/co in viral replication(1).oxidative stress became emerged as a key player in the development and progression of many pathological conditions including virus-induced encephalitis. heme oxygenase-1 (ho-1) plays a crucial role in defending the body against oxidant-induced injury during inflammatory processes. therefore, we investigated the induction of ho-1 level in host cells, which may exert a beneficial effect to minimize viral replication in sk-n-sh cells. in this study, we found that enterovirus 71 (ev71) induced the g ...201121321939
estimation of the basic reproduction number of enterovirus 71 and coxsackievirus a16 in hand, foot, and mouth disease outbreaks.coxsackievirus a16 (cox a16) and enterovirus 71 (ev71) are common pathogens causing hand, foot, and mouth disease (hfmd) in pediatric population. little is known about the basic reproductive number (r0) for these enteroviruses.201121326133
mapping genetic determinants of the cell-culture growth phenotype of enterovirus 71.enterovirus 71 (ev71) is a member of the species human enterovirus a within the family picornaviridae and is a major causative agent of epidemics of hand, foot and mouth disease associated with severe neurological disease. three ev71 genogroups, designated a, b and c, have been identified, with 75-84?% nucleotide sequence similarity between them. two strains, ev71-26m (genogroup b) and ev71-6f (genogroup c), were found to have distinct cell-culture growth (26m, rapid; 6f, slow) and plaque-format ...201121346025
biochemical characterization of enterovirus 71 3d rna polymerase.an unusual enterovirus 71 (ev71) epidemic has begun in china since 2008. ev71 rna polymerases (3d(pol)) showed polymerase activity with an mn(2+). little activity was detected with co(2+), and no activity was detected with mg(2+), ca(2+), cu(2+), ni(2+), cd(2+), or zn(2+). it is a primer-dependent polymerase, and the enzyme functioned with both di- and 10-nucleotide rna primers. dna primer, dt15, increased primer activity, similar to other enterovirus 3d(pol). however, ev71 3d(pol) initiated de ...201121220056
Mutations in VP2 and VP1 capsid proteins increase infectivity and mouse lethality of enterovirus 71 by virus binding and RNA accumulation enhancement.Enterovirus 71 (EV71) is a major cause of hand-foot-and-mouth disease. EV71 infection occasionally associates with severe neurological sequelae such as brainstem encephalitis or poliovirus-like paralysis. We demonstrated that mouse-adapted strain increases infectivity, resulting in higher cytotoxicity of neuron cells and mortality to neonatal mice than a non-adapted strain. Results pointed to EV71 capsid region determining viral infectivity and mouse lethality. Mutant virus with lysine to methio ...201222078110
enterovirus 71 uses cell surface heparan sulfate glycosaminoglycan as an attachment receptor.enterovirus 71 (ev-71) infections are usually associated with mild hand, foot, and mouth disease in young children but have been reported to cause severe neurological complications with high mortality rates. to date, four ev-71 receptors have been identified, but inhibition of these receptors by antagonists did not completely abolish ev-71 infection, implying that there is an as yet undiscovered receptor(s). since ev-71 has a wide range of tissue tropisms, we hypothesize that ev-71 infections ma ...201223097443
characterization of an isotype-dependent monoclonal antibody against linear neutralizing epitope effective for prophylaxis of enterovirus 71 infection.enterovirus 71 (ev71) is the main causative agent of hand, foot and mouth disease (hfmd) and is associated with severe neurologic complications and mortalities. at present, there is no vaccine or therapeutic available for treatment.201222279543
far upstream element binding protein 1: a commander of transcription, translation and beyond.the far upstream binding protein 1 (fbp1) was first identified as a dna-binding protein that regulates c-myc gene transcription through binding to the far upstream element (fuse) in the promoter region 1.5 kb upstream of the transcription start site. fbp1 collaborates with tfiih and additional transcription factors for optimal transcription of the c-myc gene. in recent years, mounting evidence suggests that fbp1 acts as an rna-binding protein and regulates mrna translation or stability of genes, ...201222926519
molecular characterization of human enteroviruses in the central african republic: uncovering wide diversity and identification of a new human enterovirus a71 genogroup.human enteroviruses (hev) are among the most common viruses infecting humans. their circulation has been widely studied in most parts of the world but not in sub-saharan africa, where poliomyelitis remains prevalent. we report here the molecular characterization of 98 nonpoliovirus (non-pv) hev strains isolated from 93 randomly selected cell culture-positive supernatants from stool samples collected from 1997 through 2006 from children with acute flaccid paralysis living in the central african r ...201222337981
inhibition of enterovirus 71 (ev-71) infections by a novel antiviral peptide derived from ev-71 capsid protein vp1.enterovirus 71 (ev-71) is the main causative agent of hand, foot and mouth disease (hfmd). in recent years, ev-71 infections were reported to cause high fatalities and severe neurological complications in asia. currently, no effective antiviral or vaccine is available to treat or prevent ev-71 infection. in this study, we have discovered a synthetic peptide which could be developed as a potential antiviral for inhibition of ev-71. ninety five synthetic peptides (15-mers) overlapping the entire e ...201222563456
production of ev71 vaccine candidates.enterovirus 71 (ev71) is now recognized as an emerging neurotropic virus in asia and with coxsackie virus (cv) it is the other major causative agent of hand-foot-mouth diseases (hfmd). effective medications and/or prophylactic vaccines against hfmd are urgently needed. from a scientific (the feasibility of bioprocess, immunological responses and potency in animal challenge model) and business development (cost of goods) points of view, we in this review address and discuss the pros and cons of d ...201222992566
immunological evaluation and comparison of different ev71 vaccine candidates.enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are major causative agents of hand, foot, and mouth diseases (hfmds), and ev71 is now recognized as an emerging neurotropic virus in asia. effective medications and/or prophylactic vaccines against hfmd are not available. the current results from mouse immunogenicity studies using in-house standardized rd cell virus neutralization assays indicate that (1) vp1 peptide (residues 211-225) formulated with freund's adjuvant (cfa/ifa) elicited low v ...201223008736
[association of hla-g 14bp gene polymorphisms and plasma shla-g level with susceptibility to ev71 infection in children].explore the relationship between the hla-g 14bp insertion/deletion polymorphism and the infection of enterovirus 71 (ev71) for children.201223627021
[transmission and prevalence patterns of c4a evolutionary lineage of human enterovirus 71 circulating in mainland of china, 2008-2010].to understand the evolutionary relationship between the c4a evolutionary lineage of human enterovirus 71 (hev71) strains circulating in mainland of china during 2008-2010 and 2008 fuyang strains and study the prevalence and transmission patterns of 2008 fuyang strains.201223627020
[detection the pathogens and analysis the clinical characteristics in children with hand, foot and mouth disease in shanghai during 2009-2011].to investigate the epidemic characteristics of etiological agents and analyze the clinic differences in children with hand, foot and mouth diseases in shanghai.201223547454
[isolation and sequence analysis on virus of hfmd with encephalitis in yantal city].to learn about the pathogen spectrum and genetic characterization of hfmd with encephalitis in yantai city.201223547453
enterovirus 71 causes hand, foot and mouth disease outbreak in cambodia. 201223448647
[genetic characteristics of enterovirus 71 vp1 and epidemiology of hand-foot-mouth disease in xinxiang in 2011].the study was performed to examine the enterovirus 71(ev71) vp1 genetic feature and the epidemiology of hand-foot-mouth disease (hfmd) in xinxiang in 2011. real-time rt-pcr was used for the detection of pan-enterovirus, coxsackievirus a 16(ca16) and ev71 from stool specimens of hfmd. the vp1 region was amplified from 10 ev71 positive samples and the products were sequenced. ev71 genotypes were characterized by homology and phylogenetic tree analyses. additionally, epidemic data of xinxiang hfmd ...201223367569
[comparison of different molecular assays for the rapid detection of enterovirus 71 (ev71)].molecular detection of enterovirus (ev)71 rna based on pcr methods is a quick and sensitive approach. at present, different pcr-based methods for ev71 rna detection are available, but comparisons of results obtained using different approaches are limited. this study is to compare the analytical sensitivity and specificity of different real-time reverse transcription-polymerase chain reaction (rrt-pcr) and conventional reverse transcription-polymerase chain reaction (crt-pcr) assays for enterovir ...201223367568
[analysis on epidemiology and the main clinical symptoms of viral encephalitis in gansu, 2009-2011].to understand the epidemiological characteristics and the main clinical symptoms of viral encephalitis in gansu.201223363967
[etiology surveillance of hand-foot-mouth disease in henan province between 2008 and 2011].to understand etiological types and distribution features of hand-foot-mouth disease (hfmd) in henan province between 2008 and 2011.201223363860
[typing and identification of non-polio enterovirus from acute flaccid paralysis cases in ningxia, 1997-2011].to identify the serotype of 73 non-polio enterovirus (npev) strains from acute flaccid paralysis (afp) cases in ningxia province, during 1997 - 2011.201223290905
[etiological detection of severe hand-food-mouth disease and related genetic characteristics of enterovirus type 71 infection in beijing, 2010].to study the etiological detection on samples from severe hand-foot-mouth disease (hfmd) cases and the genetic characteristics of enterovirus type 71 (ev71) isolates from severe patients in beijing, 2010.201223290804
enterovirus 71-induced neurological disorders in young gerbils, meriones unguiculatus: development and application of a neurological disease model.a reliable disease model mimicking enterovirus 71 (ev71) infection in humans is essential for understanding pathogenesis and for developing a safe and effective vaccine. commonly used rodent models including mouse or rat models are not suitable for vaccine evaluation because the rodents are resistant to ev71 infection after they reach the age of 6 days. in this study, 21-day-old gerbils inoculated intraperitoneally (ip) with a non mouse-adapted ev71 strain developed neurological lesion-related s ...201223284845
evaluation of a direct reverse transcription loop-mediated isothermal amplification method without rna extraction for the detection of human enterovirus 71 subgenotype c4 in nasopharyngeal swab specimens.human enterovirus 71 (ev71) is the major causative agent of hand, foot, and mouth disease (hfmd) worldwide and has been associated with neurological complications which resulted in fatalities during recent outbreak in asia pacific region. a direct reverse transcription loop-mediated isothermal amplification (direct rt-lamp) assay using heat-treated samples without rna extraction was developed and evaluated for the detection of ev71 subgenotype c4 in nasopharyngeal swab specimens. the analytical ...201223272248
[cloning, expression and antigenic analysis of vp1-vp4 gene encoding the structural protein of coxsackie virus a16].to clone and express vp1-vp4 genes encoding the structural proteins of coxsackie virus a16 and analyze the antigenicity of the expressed recombinant proteins.201223268395
development and characterization of a stable egfp enterovirus 71 for antiviral screening.enterovirus 71 (ev71) is one of the major causative agents for hand, foot, and mouth disease. there is currently no clinically approved vaccine or antiviral treatment for ev71 infection. to facilitate antiviral drug discovery, we developed an infectious cdna clone of an epidemic strain of ev71 and a stable egfp reporter ev71. the reporter virus was generated by engineering the egfp gene between the 5' untranslated region and vp4 gene of the ev71 genome. vero cells transfected with the cdna clone ...201223267829
evaluation of human enterovirus 71 and coxsackievirus a16 specific immunoglobulin m antibodies for diagnosis of hand-foot-and-mouth disease.abstract: background: hand-foot-and-mouth disease (hfmd) is caused mainly by the human enterovirus type 71 (hev71) and the coxsackievirus a group type 16 (cva16). large outbreaks of disease have occurred frequently in the asia-pacific region. reliable methods are needed for diagnosis of hfmd in childen. igm-capture elisa, with its notable advantages of convenience and low cost, provides a potentially frontline assay. we aimed to evaluate the newly developed igm-capture elisas for hev71 and cva1 ...201222234169
enterovirus 71 disrupts interferon signaling by reducing the interferon receptor i.the recent outbreak of enterovirus 71 (ev71) infected millions of children and caused over 1,000 deaths. to date, neither effective vaccine nor antiviral treatment is available for ev71 infection. interferons (ifns) have been successfully applied for treating patients such as hepatitis b and c viral infections for decades but failed to treat ev71 infections. here, we provide the evidence that ev71 antagonizes type i ifn signaling by reducing the level of interferon receptor 1 (ifnar1). we show t ...201222258259
in vitro and in vivo evaluation of ribavirin and pleconaril antiviral activity against enterovirus 71 infection.enterovirus 71(ev71) causes recurring outbreaks of hand, foot and mouth disease and encephalitis leading to complications or death in young children. more effective antiviral drugs are needed to prevent or reduce ev71-related disease and complications. however, there are no standard models currently in use to evaluate activity against ev71 infection both in vitro and in vivo. in this study, the activity of ribavirin and pleconaril against ev71 infection was evaluated in two models. an in vitro e ...201222245989
detection of human enterovirus 71 and coxsackievirus a16 in children with hand, foot and mouth disease in china.the aims of the present study were to investigate the genetic characteristics of enterovirus 71 (ev71) and coxsackievirus a16 (cva16) strains in china and to evaluate the relationship between the genotypes of cva16 and ev71 and their geographical distribution. a total of 399 stool specimens were collected from children with symptoms of hand, foot and mouth disease (hfmd) in zhejiang province. the presence of enteroviruses was determined ...201222218731
distribution of enteroviruses in hospitalized children with hand, foot and mouth disease and relationship between pathogens and nervous system complications.abstract: background: to explore the relationship between enteroviruses and hospitalized children with hand, foot and mouth disease (hfmd) complicated with nervous system disease. 234 hospitalized hfmd patients treated in shengjing hospital, liaoning province were analyzed retrospectively. based on the presence and severity of nervous system disease, the patients were grouped as follows: general patients, severely ill patients, critically ill patients and fatal patients. based on the detected p ...201222230340
detection of human enterovirus 71 reverse transcription loop-mediated isothermal amplification (rt-lamp).aims:  in this study, a one-step, single-tube reverse transcription loop-mediated isothermal amplification (rt-lamp) assay was developed and validated for the detection of human enterovirus 71 (ev71), the major aetiological agent of hand, foot and mouth disease (hfmd). methods and results:  reverse transcription loop-mediated isothermal amplification assay was optimized to amplify vp1 gene in the presence of a specific primer set and bst dna polymerase at an isothermal temperature of 63°c for 1  ...201222256968
Modification of the untranslated regions of human enterovirus 71 impairs growth in a cell-specific manner.Human enterovirus 71 (HEV71) is the causative agent of hand, foot, and mouth disease and associated acute neurological disease. At present, little is known about the genetic determinants of HEV71 neurovirulence. Studies of related enteroviruses have indicated that the untranslated regions (UTRs), which control virus-directed translation and replication, also exert significant influence on neurovirulence. We used an infectious cDNA clone of a subgenogroup B3 strain to construct and characterize c ...201222031931
MEK1-ERKs signal cascade is required for the replication of Enterovirus 71 (EV71).The role of the MEK1-ERK signaling cascade in the replication cycle of Enterovirus 71 (EV71), the primary cause of hand, foot and mouth disease (HFMD), has been analyzed. In vitro infection with EV71 induced a biphasic activation of ERK. The two phases of activation appeared to be triggered by different mechanisms, with the first phase being activated by the binding of viral particles to the membrane receptor of host cells and the second probably being in response to the production of new virus ...201222101247
outbreak of hand, foot and mouth disease/herpangina associated with coxsackievirus a6 and a10 infections in 2010, france: a large citywide, prospective observational study.hand, foot and mouth disease (hfmd) and herpangina (ha) are frequently caused by several distinct serotypes belonging to the human enterovirus a species (heva). enterovirus 71 is considered as a significant public health threat because of rare but fatal neurological complications. a sentinel surveillance system involving paediatricians from clermont-ferrand (france) was set up to determine the clinical and epidemiological characteristics of hfmd/ha associated with enterovirus infections. a stand ...201222404077
occurrence of hand-foot-and-mouth disease pathogens in domestic sewage and secondary effluent in xi'an, china.hand, foot and mouth disease (hfmd), caused by a group of enteric viruses such as enterovirus 71 (ev71), coxsackievirus a16 (cva16) and coxsackievirus a10 (cva10), is heavily epidemic in east asia. this research focused on investigating the occurrence of hfmd pathogens in domestic sewage and secondary effluent before disinfection in a wastewater treatment plant (wwtp) in xi'an, the largest megacity in northwest china. in order to simultaneously detect all three hfmd pathogens, a semi-nested rt-p ...201222446307
pilot scale production of highly efficacious and stable enterovirus 71 vaccine candidates.enterovirus 71 (ev71) has caused several epidemics of hand, foot and mouth diseases (hfmd) in asia and now is being recognized as an important neurotropic virus. effective medications and prophylactic vaccine against ev71 infection are urgently needed. based on the success of inactivated poliovirus vaccine, a prototype chemically inactivated ev71 vaccine candidate has been developed and currently in human phase 1 clinical trial.201222529942
coxsackievirus mutants that can bypass host factor pi4kiiiβ and the need for high levels of pi4p lipids for replication.rna viruses can rapidly mutate and acquire resistance to drugs that directly target viral enzymes, which poses serious problems in a clinical context. therefore, there is a growing interest in the development of antiviral drugs that target host factors critical for viral replication, since they are unlikely to mutate in response to therapy. we recently demonstrated that phosphatidylinositol-4-kinase iiiβ (pi4kiiiβ) and its product phosphatidylinositol-4-phosphate (pi4p) are essential for replica ...201222945356
immunological and biochemical characterization of coxsackie virus a16 viral particles.coxsackie virus a16 (cva16) infections have become a serious public health problem in the asia-pacific region. it manifests most often in childhood exanthema, commonly known as hand-foot-and-mouth disease (hfmd). there are currently no vaccine or effective medical treatments available.201223226233
rapid and sensitive identification of rna from the emerging pathogen, coxsackievirus a6.hand, foot and mouth disease (hfmd) is caused by members of the family picornaviridae in the genus enterovirus. it has been reported that coxsackievirus a6 (cva6) infections are emerging as a new and major cause of epidemic hfmd. sporadic hfmd cases positive for cva6 were detected in the mainland of china in recent years. to strengthen the surveillance of cva6 infections and outbreak control, the clinical diagnosis is urgently needed to distinguish the cva6 infection disease from other infection ...201223194501
enterovirus 71 blocks selectively type i interferon production through the 3c viral protein in mice.type i interferons (ifns) represent an essential innate defense mechanism for controlling enterovirus 71 (ev 71) infection. mice inoculated with ev 71 produced a significantly lower amount of type i ifns than those inoculated with poly (i:c), adenovirus type v, or coxsackievirus b3 (cb3). ev 71 infection, however, mounted a proinflammatory response with a significant increase in the levels of serum and brain interleukin (il)-6, monocyte chemoattractant protein-1, tumor necrosis factor, and ifn-γ ...201222997081
cellular receptors for human enterovirus species a.human enterovirus species a (hev-a) is one of the four species of hev in the genus enterovirus in the family picornaviridae. among hev-a, coxsackievirus a16 (cva16) and enterovirus 71 (ev71) are the major causative agents of hand, foot, and mouth disease (hfmd). some other types of hev-a are commonly associated with herpangina. although hfmd and herpangina due to hev-a are common febrile diseases among infants and children, ev71 can cause various neurological diseases, such as aseptic meningitis ...201222470371
human scarb2-dependent infection by coxsackievirus a7, a14, and a16 and enterovirus 71.human enterovirus species a (hev-a) consists of at least 16 members of different serotypes that are known to be the causative agents of hand, foot, and mouth disease (hfmd), herpangina, and other diseases, such as respiratory disease and polio-like flaccid paralysis. enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are the major causative agents of hfmd. cva5, cva6, cva10, and cva12 mainly cause herpangina or are occasionally involved with sporadic cases of hfmd. we have previously shown tha ...201222438546
comparative genetic analysis of vp4, vp1 and 3d gene regions of enterovirus 71 and coxsackievirus a16 circulating in malaysia between 1997-2008.three genomic regions, vp4 capsid, vp1 capsid and 3d rna polymerase of human enterovirus 71 (ev-71) and coxsackievirus a16 (cv-a16) were sequenced to understand the evolution of these viruses in malaysia. a total of 42 ev-71 and 36 cv-a16 isolates from 1997- 2008 were sequenced. despite the presence of many ev-71 subgenotypes worldwide, only subgenotypes b3, b4, b5, c1 and c2 were present in malaysia. importation of other subgenotypes such as c3, c4/d and c5 from other countries was infrequent. ...201223018509
etiologic and epidemiologic analysis of hand, foot, and mouth disease in guangzhou city: a review of 4,753 cases.this study aimed to review etiological and epidemiological data for hand, foot, and mouth disease (hfmd) cases that occurred between 2008 and 2010 in guangzhou city, to help develop and implement precautionary measures applicable for future outbreaks.201222964289
identification and characterization of a monoclonal antibody recognizing the linear epitope rvadvi on vp1 protein of enterovirus 71.several large outbreaks of hand-foot-mouth disease (hfmd) have occurred in the asian-pacific region since 1997, with enterovirus 71 (ev71) and/or coxsackievirus a16 (cav16) as the main causative agents. despite the close genetic relationship between the two viruses, only ev71 is associated with severe clinical manifestations and deaths. effective antiviral treatment and vaccines are not available. high-quality monoclonal antibodies (mabs) are necessary to improve the accuracy of the diagnosis of ...201222930511
antigenic diversity of enteroviruses associated with nonpolio acute flaccid paralysis, india, 2007-2009.because of the broadened acute flacid paralysis (afp) definition and enhanced surveillance, many nonpolio afp (np-afp) cases have been reported in india since 2005. to determine the spectrum of nonpolio enterovirus (npev) serotypes associated with np-afp from polio-endemic and -free regions, we studied antigenic diversity of afp-associated npevs. of fecal specimens from 2,786 children with np-afp in 1 polio-endemic and 2 polio-free states, 823 (29.5%) were positive for npevs in rd cells, of whic ...201223092622
[outbreak of acute enterovirus intestinal infection in sakhalin region in august 2010].the investigation of cases of acute intestinal infections in the sakhalin region of russia in august, 2010 is described. epidemiological and molecular biological studies were conducted. after initial pcr screening and determining the nucleotide sequences of the positive samples the following enteroviruses were found: coxsackie a2 - 42 samples (45%), coxsackie a4--31 sample (34%), enterovirus 71--6 samples (6,5%), coxsackievirus b5--6 samples (6,5%), coxsackie b3--4 samples (4%) and coxsackie b1- ...201222642180
evidences for intertypic and intratypic recombinant events in ev71 of hand, foot and mouth disease during an epidemic in hubei province, china, 2011.humane enterovirus 71 (hev 71) is a common contagious agent of hand, foot and mouth disease (hfmd) which is normally mild but can caused deaths and severe neurological complications. in april 2011, an unpredicted hfmd outbreak in xiangyang city of hubei province in china resulted in a high aggregation of hfmd cases including fatal cases and many severe cases. in this study, 71 clinical specimens were collected according to the different symptoms and rna extraction and rt-pcr amplification were p ...201222922556
a novel minicircle vector based system for inhibting the replication and gene expression of enterovirus 71 and coxsackievirus a16.enterovirus 71 (ev 71) and coxsackievirus a16 (ca 16) are two major causative agents of hand, foot and mouth disease (hfmd). they have been associated with severe neurological and cardiological complications worldwide, and have caused significant mortalities during large-scale outbreaks in china. currently, there are no effective treatments against ev 71 and ca 16 infections. we now describe the development of a novel minicircle vector based rna interference (rnai) system as a therapeutic approa ...201222921338
replication kinetics of coxsackievirus a16 in human rhabdomyosarcoma cells.coxsackievirus a16 (cva16), together with enterovirus type 71 (ev71), is responsible for most cases of hand, foot and mouth disease (hfmd) worldwide. recent findings suggest that the recombination between cva16 and ev71, and the co-circulation of these two viruses may have contributed to the increase of hfmd cases in china over the past few years. it is therefore important to further understand the virology, epidemiology, virus-host interactions and host pathogenesis of cva16. in this study, we ...201222899429
encephalomyocarditis virus viroporin 2b activates nlrp3 inflammasome.nod-like receptors (nlrs) comprise a large family of intracellular pattern- recognition receptors. members of the nlr family assemble into large multiprotein complexes, termed the inflammasomes. the nlr family, pyrin domain-containing 3 (nlrp3) is triggered by a diverse set of molecules and signals, and forms the nlrp3 inflammasome. recent studies have indicated that both dna and rna viruses stimulate the nlrp3 inflammasome, leading to the secretion of interleukin 1 beta (il-1β) and il-18 follow ...201222916014
seroepidemiology of human enterovirus71 and coxsackievirusa16 in jiangsu province, china.the major etiology of hand, foot and mouth disease (hfmd) is infection with human enterovirus a (hev-a). among subtypes of hev-a, coxsackievirusa16 (coxa16) and enterovirus 71 (ev71) are major causes for recurrent hfmd among infants and children in jiangsu province, mainland china. here, we analyzed maternal antibodies between prenatal women and their neonates, to determine age-specific seroprevalence of human ev71 and coxa16 infections in infants and children aged 0 to 15 years. the results may ...201223102275
challenges to licensure of enterovirus 71 vaccines.human enteroviruses usually cause self-limited infections except polioviruses and enterovirus 71 (ev71), which frequently involve neurological complications. ev71 vaccines are being evaluated in humans. however, several challenges to licensure of ev71 vaccines need to be addressed. firstly, ev71 and coxsackievirus a (ca) are frequently found to co-circulate and cause hand-foot-mouth disease (hfmd). a polyvalent vaccine that can provide protection against ev71 and prevalent ca are desirable. seco ...201222953003
[etiology of hand-foot-and-mouth disease seen in nanjing in 2010 and molecular characteristics analysis of ev71].to study the etiological agent of hand-foot-and-mouth disease (hfmd), and to genetically characterize enterovirus 71 (ev71) isolated from clinical specimens of hfmd patients in nanjing in 2010.201222801226
[epidemiology and etiology of hand-foot-and-mouth disease seen in jiangsu province from 2008 to 2010].to analyze the etiological and epidemiological characteristics of hand-foot-and-mouth disease (hfmd) seen in jiangsu province from 2008 to 2010, and provide evidence for its prevention and control.201222801225
antiviral ability of kalanchoe gracilis leaf extract against enterovirus 71 and coxsackievirus a16.pandemic infection or reemergence of enterovirus 71 (ev71) and coxsackievirus a16 (cva16) occurs in tropical and subtropical regions, being associated with hand-foot-and-mouth disease, herpangina, aseptic meningitis, brain stem encephalitis, pulmonary edema, and paralysis. however, effective therapeutic drugs against ev71 and cva16 are rare. kalanchoe gracilis (l.) dc is used for the treatment of injuries, pain, and inflammation. this study investigated antiviral effects of k. gracilis leaf extr ...201222666293
antigenic characteristics of the complete and truncated capsid protein vp1 of enterovirus 71.the complete vp1 protein of enterovirus 71 (ev71) and a series of truncations were expressed in escherichia coli and their antigenic characteristics were studied. immunoblot analysis showed the major immunoreactive region of the vp1 protein was located in the n-terminal portion at position of amino acid (aa) 1-100. the complete vp1 possessed strong cross-reactivity with antisera against coxsackievirus a16 (ca16) and echovirus 6 (echo6), while the truncated fragment at position 1-100 aa only had ...201222659489
simultaneous detection of enterovirus 71 and coxsackievirus a16 using dual-colour upconversion luminescent nanoparticles as labels.we highlight a novel fluorescence analysis for sensitive and selective detection of ev-71 and cv-a16 by combining labelling technology based on dual-colour upconversion fluorescence nanoparticles (ucnps) with magnetic bioseparation and concentration technology based on magnetite nanoparticles (mnps).201222498910
simultaneous determination of human enterovirus 71 and coxsackievirus b3 by dual-color quantum dots and homogeneous immunoassay.human enterovirus 71 (ev71) and coxsackievirus b3 (cvb3) have high risks for morbidity and mortality. a virus quantitation immunoassay has been proposed by employing two colored quantum dots (qds), antibodies of the virus, and graphene oxide (go). the qds are streptavidin-conjugated quantum dots (sa-qds), and the antibodies are biotinylated antibodies. biotinylated ev71 antibody (ab1) was associated with 525 nm green colored sa-qds via biotin-streptavidin interaction forming qds-ab1, whereas bio ...201222390751
copi is required for enterovirus 71 replication.enterovirus 71 (ev71), a member of the picornaviridae family, is found in asian countries where it causes a wide range of human diseases. no effective therapy is available for the treatment of these infections. picornaviruses undergo rna replication in association with membranes of infected cells. copi and copii have been shown to be involved in the formation of picornavirus-induced vesicles. replication of several picornaviruses, including poliovirus and echovirus 11 (ev11), is dependent on cop ...201222662263
[chest x-ray findings in children with enterovirus 71 infection].to study the characteristics of the chest x-ray images in children infected with enterovirus 71.201222738450
increased frequency of th17 cells in the peripheral blood of children infected with enterovirus 71.enterovirus 71 (ev71) affects the health of young children globally causing severe neurologic diseases. the relationship between ev71 infection and t helper type 17 (th17) has not been described, although this new th subset or interleukin-17 (il-17) has been reported to be associated with other viral infections. the purpose of the current study was to describe the immune profile involving th17 cells, neutrophils, and related factors and to speculate on the possible immunopathogenesis of ev71 inf ...201222431024
safety and immunogenicity of a novel human enterovirus 71 (ev71) vaccine: a randomized, placebo-controlled, double-blind, phase i clinical trial.there is an urgent need for a novel vaccine that is effective against human enterovirus 71 (ev71) outbreaks. a double-blind, randomized controlled study was to evaluate the safety and immunogenicity of a human ev71 vaccine in healthy adults, children and infants. the vaccine dosages were 200 u and 400 u for children and adults, and 100 u, 200 u and 400 u for infants. subjects were randomized to receive different dosages of the vaccine or placebo. adults received intramuscular injection on days 0 ...201222426327
[experimental studies on infant tupaia belangeri chineses with ev71 infection].tupaia belangeri are small mammals with a squirrel-like appearance; they were formerly classified under the primates order despite the lack of derived features characteristic of primates. given that t. belangeri are easy to raise, cheap to maintain, and have a small body size, a high reproductive rate, and close affinity to primates, these animals would be used as an alternative to primates in biomedical research. three-month old t. belangeri chineses were infected with enterovirus 71 (ev71) via ...201222345002
antiviral effect of geraniin on human enterovirus 71 in vitro and in vivo.human enterovirus 71 infection causes hand, foot and mouth disease in children under 6 years of age and has caused mortalities in large-scale outbreaks in the asia-pacific region. no effective vaccine or antiviral drugs currently exist against enterovirus 71 in the clinic. in this study, we investigated the antiviral effect of geraniin on enterovirus 71 both in vitro and in vivo. the results showed that geraniin effectively inhibited virus replication in rhabdomyosarcoma cells with an ic(50) of ...201222342145
screening and detection of human enterovirus 71 infection by a real-time rt-pcr assay in marseille, france, 2009-2011.enterovirus-positive samples diagnosed in marseille (january 2009 to september 2011) were screened for ev71 by real-time rt-pcr. ev71 was detected in three children below the age of 2 years with no history of overseas travel; two of these cases were associated with severe clinical presentation. viruses demonstrated genetic similarity to other european genogroup c2 strains. strain mrs/09/3663 complete sequencing revealed 97.6% identity across the entire genome with a 2008 singapore isolate, witho ...201222332991
association of interleukin 10 and interferon gamma gene polymorphisms with enterovirus 71 encephalitis in patients with hand, foot and mouth disease.enterovirus 71 (ev71) is one of the common causative agents of hand, foot and mouth disease (hfmd), and is associated with several outbreaks with neurological complications including encephalitis. this study investigated the polymorphisms of interferon gamma (ifn-γ)+874 t/a and interleukin 10 (il-10)-1082 g/a in 65 chinese patients with ev71 encephalitis and 113 chinese hfmd patients without complications. the polymorphisms of ifn-γ+874 t/a and il-10-1082 g/a were determined by polymerase chain ...201222263663
a colorimetric-based accurate method for the determination of enterovirus 71 titer.the 50 % tissue culture infectious dose (tcid50) is still one of the most commonly used techniques for estimating virus titers. however, the traditional tcid50 assay is time consuming, susceptible to subjective errors and generates only quantal data. here, we describe a colorimetric-based approach for the titration of enterovirus 71 (ev71) using a modified method for making virus dilutions. in summary, the titration of ev71 using mtt or mts staining with a modified virus dilution method decrease ...201224293817
enterovirus 71-associated hand, foot, and mouth disease, southern vietnam, 2011.we prospectively studied 3,791 children hospitalized during 2011 during a large outbreak of enterovirus 71-associated hand, foot, and mouth disease in vietnam. formal assessment of public health interventions, use of intravenous immunoglobulin and other therapies, and factors predisposing for progression of disease is needed to improve clinical management.201223194699
differential apoptosis gene expressions of rhabdomyosarcoma cells in response to enterovirus 71 infection.enterovirus 71 (ev71) infection can induce the apoptosis of infected cells. the aim of this study is to explore the effect of ev71 infection on apoptosis mechanisms in virus-infected human rhabdomyosarcoma (rd) cells.201223191987
[multiple viral transmission chains of enterovirus 71 co-circulated in jilin province during 2009-2010].to analyze the genetic characterization of enterovirus type71 (ev71) associated with hand foot and mouth disease (hfmd) epidemics in jilin province, during 2009-2010.201223189842
[infection mechanism of enterovirus 71].identification of a specific viral receptor is important for understanding the virus infection mechanism. i identified p-selectin glycoprotein ligand-1 (psgl-1) as one of the functional receptors for enterovirus 71 (ev71), a pathogen that causes hand, foot, and mouth disease. psgl-1, which belongs to the sialomucin family, is a transmembrane protein mainly expressed on leukocytes. tyrosine sulfation in the n-terminal region of psgl-1 is critical for psgl-1's capacity to bind ev71. the identifica ...201223189832
comparative analysis of the immunogenicity and protective effects of inactivated ev71 vaccines in mice.enterovirus 71 (ev71) is the major causative agent of hand, foot, and mouth disease (hfmd). three inactivated ev71 whole-virus vaccines of different strains developed by different manufacturers in mainland china have recently entered clinical trials. although several studies on these vaccines have been published, a study directly comparing the immunogenicity and protective effects among them has not been carried out, which makes evaluating their relative effectiveness difficult. thus, properly c ...201223029378
cross-reactive neutralizing antibody epitopes against enterovirus 71 identified by an in silico approach.currently, infections of hand, foot and mouth disease (hfmd) due to human enterovirus 71 (ev71) cannot be prevented or treated, as there are no suitable vaccines or antiviral drugs. this study aimed to identify potential vaccine candidates for ev71 using in silico analysis of its viral capsid proteins. a combined in silico approach utilizing computational hidden markov model (hmm), propensity scale algorithm, and artificial learning, identified three 15-mer structurally conserved b-cell epitope ...201223022400
[human enterovirus 71 (ev71) resisted type i interferon induced antiviral effect].to investigate human enterovirus 71 (ev71) resistance to type i interferon induced antiviral effect.201223002545
[methyl 3, 4-dihydroxyphenylacetate prevents enterovirus 71 proliferation in rhabdomyosarcoma cells].this article presented the inhibitory activity of methyl 3, 4-dihydroxyphenylacetate on the enterovirus 71 (ev71) infection. the ev71 vp1 capsid protein expression levels were analyzed with western blotting. results revealed that the compound is able to inhibit ev71 replication in rhabdomyosarcoma (rd) cells. after being incubated with the compound at a concentration of 0.01 microg x microl(-1) for 48 h, the level of ev71 vp1 mrna in rd cells decreased by (76.83 +/- 2.47)%. the cytotoxic activit ...201223227560
infectious myelopathies.infections and secondary inflammatory changes play an important role in spine pathology leading to myelopathy or myelitis. to achieve optimal clinical outcomes and accurate prognosis, physicians must promptly recognize these disorders. this review provides a contemporary overview of the major pathogens known to cause myelopathic symptoms and focuses on unique clinical syndromes and signs to aid the differential diagnosis and further workup. this article will help neurologists to consider infecti ...201223221845
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